Hypothalamic slices prepared from female rats in various hormonal conditions were incubated in vitro in the presence or absence of 10 microM norepinephrine (NE), and cyclic AMP content was measured. Slices from animals in late diestrus or with exogenous estrogen treatment responded to NE with marked elevations of cyclic AMP in all but the posterior hypothalamus. Slices from rats sacrificed in late proestrus or following estrogen plus progestin administration showed little or no NE-stimulated cyclic AMP accumulation.